Immunovirological and environmental screening reveals actionable risk factors for fatal COVID-19 during post-vaccination nursing home outbreaks
Authors: Lize Cuypers, Els Keyaerts, Samuel Leandro Hong, Sarah Gorissen, Soraya Maria Menezes, Marick Starick, Jan Van Elslande, Matthias Weemaes, Tony Wawina-Bokalanga, Joan Marti-Carreras, Bert Vanmechelen, Bram Van Holm, Mandy Bloemen, Jean-Michel Dogne, François Dufrasne, Keith Durkin, Jean Ruelle, Ricardo De Mendonca, Elke Wollants, Pieter Vermeersch, Ruddy Wattiez, Michael Peeters, Kate Bakelants, Sarah Denayer, François E. Dufrasne, Cécile Meex, Laurent Gillet, Maria Artesi, Marie-Pierre Hayette, Sébastien Bontems, Vincent Bours, Claire Gourzonès, Olivier Ek, Fabrice Bureau, Benoit Kabamba, Jean-Luc Gala, Bertrand Bearzatto, Jérôme Ambroise, Arnaud Marchant, Coralie Henin, Benoit Haerlingen, Ricardo de Mendonca, Marie-Luce Delforge, Carl Vael, Lynsey Berckmans, Philippe Selhorst, Kevin K. Ariën, Sonia Van Dooren, Bruno Hinckel, Hideo Imamura, Toon Janssen, Ben Caljon, Oriane Soetens, Denis Piérard, Thomas Demuyser, Charlotte Michel, Olivier Vandenberg, Sigi van den Wijngaert, Giulia Zorzi, Philippe Van Lint, Walter Verstrepen, Reinout Naesens, Sarah Van Lent, Pascale Hilbert, Sylvain Brohée, Pierre-Emmanuel Léonard, Deniz Karadurmus, Jeremie Gras, Damien Féret, Barbara Lambert, Anne Vankeerberghen, Astrid Holderbeke, Hans De Beenhouwer, Lien Cattoir, Christine Lammens, Basil Britto Xavier, Marie Le Mercier, Jasmine Coppens, Veerle Matheeussen, Herman Goossens, Geert A. Martens, Koen Swaerts, Frederik Van Hoecke, Dieter Desmet, Patrick Descheemaeker, Pierre Bogaerts, Jonathan Degosserie, Olivier Denis, Te-Din Huang, Dagmar Obbels, Hanne Valgaeren, Johan Frans, Annick Smismans, Paul-Emile Claus, Denise Veltman, Truus Goegebuer, Ann Lemmens, Bea Van den Poel, Sonja De Bock, Wim Laffut, Ellen Van Even, Jos Van Acker, Charlotte Verfaillie, Elke Vanlaere, Klara De Rauw, Luc Waumans, Britt Van Meensel, Reinoud Cartuyvels, Marijke Raymaekers, Bruno Verhasselt, Jorn Hellemans, Merijn Vanhee, Marijke Reynders, Caroline Boulouffe, Achille Djiena, Caroline Broucke, Boudewijn Catry, Katrien Lagrou, Marc Van Ranst, Johan Neyts, Guy Baele, Piet Maes, Emmanuel André, Simon Dellicour, Johan Van Weyenbergh
Journal: Nature Aging (2023)

Coronavirus Disease 2019 (COVID-19) vaccination has resulted in excellent protection against fatal disease, including in older adults. However, risk factors for post-vaccination fatal COVID-19 are largely unknown. We comprehensively studied three large nursing home outbreaks (20-35% fatal cases among residents) by combining severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) aerosol monitoring, whole-genome phylogenetic analysis and immunovirological profiling of nasal mucosa by digital nCounter transcriptomics. Phylogenetic investigations indicated that each outbreak stemmed from a single introduction event, although with different variants (Delta, Gamma and Mu). SARS-CoV-2 was detected in aerosol samples up to 52 d after the initial infection. Combining demographic, immune and viral parameters, the best predictive models for mortality comprised IFNB1 or age, viral ORF7a and ACE2 receptor transcripts. Comparison with published pre-vaccine fatal COVID-19 transcriptomic and genomic signatures uncovered a unique IRF3 low/IRF7 high immune signature in post-vaccine fatal COVID-19 outbreaks. A multi-layered strategy, including environmental sampling, immunomonitoring and early antiviral therapy, should be considered to prevent post-vaccination COVID-19 mortality in nursing homes.